1. Field of the Invention
This invention relates to a specific antibody-containing substance which is produced from an egg of a hen immunized against a selected antigen and which contains an antibody specific for the antigen, as well as a method of the production and use thereof. The present invention also relates to a substance which is produced from an egg of a hen immunized against a selected antigen and which contains a transfer factor-like component specific for the antigen, as well as a method of the production and use thereof.
2. Description of the Prior Art
U.S. Pat. No. 4,402,938 (Collins et al.) discloses a method which comprises introducing pre-partum an antigen into the udder of an ungulate, collecting the colostrum and milk produced following the colostrum, removing the fat and solids from the colostrum and milk so that only whey remains, and passing the whey through a filter having a pore size of about 0.2 microns in an ultrafiltration unit to yield as a filtrate a product which contains an unknown food factor having a molecular weight on the order of 1200 or less. According to the method, the antigen can be selected from pollen, bacteria, viruses, molds, allergens, blood from sick animals, sperm, and toxins. The product which contains the above food factor is useful as a nutrition supplement for animals.
However, according to the above method, the antigen must be administered to the ungulate during the last month of gestation, and it is critical to collect the colostrum which is produced for a very limited period, usually a few days, after parturition. Thus, the production of the above-mentioned food factor in a large amount necessitates a vast farm, and it is very difficult to use such a vast farm for constant practice of the above method in countries having limited land such as Japan or the U.K.
In addition, the method disclosed in the above U.S. Pat. involves very complicated procedures in that the colostrum and the subsequently-collected milk have to be treated separately and they must be frozen for a period as long as 60 days or more in order to precipitate and remove the solids.
The above U.S. Pat. also describes that the product obtained by the ultrafiltration with a filter having a pore size of about 0.2 microns may contain, in addition to the food factor, B lysin, conglutinin, interferon, lactoferrin, lactoperoxidase, B lymphocytes, T lymphocytes, lysozyme, macrophages, polypeptides, properdin, and thiocyanate, while proteins, globulins, and other large molecules having a molecular weight on the order of 1200 or more are removed from the product. These large molecules which are removed from the product and not used in the above method comprise beneficial active substances such as globulins, which contain an antibody specific for the antigen used in the immunization, and such specific antibody has a capability of protecting an animal when it is exposed to the same antigen.
It is well known in the art that when a specific antibody produced within the body of an animal by immunization against an antigen is administered to another animal, the animal to which the specific antibody is administered administered is effectively protected from attacks or infections by the same antigen as that used in the immunization since it is passively immunized against the antigen by the administration of the specific antibody which is active against the antigen. However, if the animal to which the antibody is administered and the immunized animal are not of the same species, repeated administrations of the antibody to the animal may cause anaphylactic shock due to a specific reaction with a heteroantibody formed in the body of the animal by the first administration. For this reason, such protection achieved by passive immunization with a heterogeneous antibody is generally applied for therapeutical purposes only to emergent situations, for example, the treatment of tetanus or snake bite.
Japanese Patent Laid-Open Application No. 60-248628 describes that a specific antibody or a specific antibody-containing fraction separated from an egg of a fowl or milk of a bovid which has been immunized against an antigen can be used for heterogeneous passive immunization of an animal against attacks by the same antigen as used in the immunization provided that the animal has acquired resistance to heterogeneous antibodies of the fowl or bovid by feeding the animal with a substance containing the heterogeneous antibodies such as milk or eggs for a long period in the range of 30 to 90 days. In Example 2 of that laid-open application, an ovular antibody-containing fraction was injected twice into rabbits which had not acquired resistance to the antibody. As a result, all the animals died due to anaphylactic shock.
Thus, the method of passive immunization disclosed in the above laid-open application requires a long period of at least 30 days before an animal is treated by the passive immunization using an ovular or bovine antibody. This means that it is very difficult to apply the method to actual treatment of infectious diseases. In addition, since the period required to acquire resistance to an antibody largely depends on the species, age, and health of the animal, the above method always involves the risk that it induces a serum sickness or even anaphylactic shock by a premature, repeated administration of the antibody.
There is no experimental data in the above Japanese laid-open application which demonstrate any therapeutical effect of administration of a specific antibody to an animal which has acquired resistance to the antibody. The only therapeutical experiment is shown in Example 3 of the laid-open application, in which an ovular antibody against Streptococcus mutans (Serotype C) was repeatedly administered per os. to germ-free rats which had not acquired resistance to ovular antibodies, and after 20 days the animals were challenged by bacteria of the same strain. The results were evaluated by the number of plaques found in molar teeth. However, there were no statistically significant differences between the results for the administered group and the control group. Furthermore, the experiment was conducted in germ-free rats which do not exist naturally by oral administration thereto of S. mutans, a bacterium which acts on cariogenesis in humans rather than rats. Therefore, the experiments do not provide reliable information on therapeutical effect which is attained by administration of the antibody or antibody-containing fraction disclosed in the laid-open application.
It is known that many infectious diseases in livestock and poultry such as pigs and fowls can be prevented by oral administration of an antibody against the bacterium which induces the disease. For this purpose, a number of methods of preparing or administering a substance which contains an antibody or antibody-like factor have been proposed in the art See, for example, the above-mentioned U.S. Pat. No. 4,402,938, and U.S. Pat. Nos. 3,984,539, and 4,284,623. However, most of the known methods use serum, colostrum, or milk from a cow to produce an antibody or antibody like factor. Therefore, these methods cannot be performed readily and conveniently in Japan or other countries having limited land, and the product thus produced is expensive.
In addition to prevention of infectious diseases in animals, a substance which contains a specific antibody or antibody-like factor has prospective usefulness as additives in foods for livestock and poultry, cosmetics, and medicines, and in the field of serodiagnosis Accordingly, it is desired to provide an antibody or antibody-like factor specific for a selected antigen or a substance containing such an antibody or antibody like factor which can be produced in large amounts and inexpensively.